BACKGROUND:Promoting skin wound healing is a huge challenge facing global public health.To promote faster and higher-quality wound healing,it is necessary to explore more advantageous dressings to address this problem.OBJECTIVE:To investigate the hemostatic properties of acellular dermal matrix hydrogel and its effect on skin wound healing.METHODS:(1)Acellular dermal matrix hydrogel was prepared,and the differences in microscopic morphology and main components between it and acellular dermal matrix were analyzed.(2)Acellular dermal matrix hydrogel and chitosan hydrogel were used to cover the femoral artery puncture site of rats,and the bleeding quality and coagulation time were recorded.Acellular dermal matrix hydrogel and chitosan hydrogel were mixed with rat anticoagulated blood,and the coagulation index within 30 minutes was detected.(3)A full-thickness skin defect model with a diameter of 12 mm was made on the back of 18 SD rats,and they were randomly divided into 3 groups,with 6 rats in each group:the model group used PBS to clean the wound,and the control group and the experimental group used chitosan hydrogel and acellular dermal matrix hydrogel to cover the wound,respectively.The hydrogel dressing was changed every day,and the treatment was continued for 14 days,and the wound healing was observed.On day 3 after modeling,immunofluorescence staining of inducible nitric oxide synthase(M1 macrophages)and CD206(M2 macrophages)was performed on the wound surface.On day 14 after modeling,hematoxylin-eosin staining,Masson staining,and CD31 immunohistochemical staining were performed on the wound surface.RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the acellular dermal matrix hydrogel had a porous structure,and the Fourier transform infrared spectrum showed that it had the same main components as the acellular dermal matrix.(2)Both acellular dermal matrix hydrogel and chitosan hydrogel had obvious hemostatic ability in vivo.In the in vitro coagulation experiments,the coagulation index of acellular dermal matrix hydrogel was significantly higher than that of chitosan hydrogel.(3)In the rat skin full-thickness defect model,both acellular dermal matrix hydrogel and chitosan hydrogel could improve the wound healing rate.Hematoxylin-eosin and Masson staining results showed that acellular dermal matrix hydrogel could reduce the infiltration of inflammatory cells in the center of the wound.Both acellular dermal matrix hydrogel and chitosan hydrogel could decrease scar width and increase collagen deposition rate.CD31 immunohistochemical staining results showed that both hydrogels could promote angiogenesis in the wound site.Immunofluorescence staining results showed that both hydrogels could reduce the proportion of M1 macrophages and increase the proportion of M2 macrophages,and the effect of acellular dermal matrix hydrogel was stronger than that of chitosan hydrogel.(4)The results show that the acellular dermal matrix hydrogel has good hemostatic properties and the ability to promote wound healing.

BACKGROUND:Promoting skin wound healing is a huge challenge facing global public health.To promote faster and higher-quality wound healing,it is necessary to explore more advantageous dressings to address this problem.OBJECTIVE:To investigate the hemostatic properties of acellular dermal matrix hydrogel and its effect on skin wound healing.METHODS:(1)Acellular dermal matrix hydrogel was prepared,and the differences in microscopic morphology and main components between it and acellular dermal matrix were analyzed.(2)Acellular dermal matrix hydrogel and chitosan hydrogel were used to cover the femoral artery puncture site of rats,and the bleeding quality and coagulation time were recorded.Acellular dermal matrix hydrogel and chitosan hydrogel were mixed with rat anticoagulated blood,and the coagulation index within 30 minutes was detected.(3)A full-thickness skin defect model with a diameter of 12 mm was made on the back of 18 SD rats,and they were randomly divided into 3 groups,with 6 rats in each group:the model group used PBS to clean the wound,and the control group and the experimental group used chitosan hydrogel and acellular dermal matrix hydrogel to cover the wound,respectively.The hydrogel dressing was changed every day,and the treatment was continued for 14 days,and the wound healing was observed.On day 3 after modeling,immunofluorescence staining of inducible nitric oxide synthase(M1 macrophages)and CD206(M2 macrophages)was performed on the wound surface.On day 14 after modeling,hematoxylin-eosin staining,Masson staining,and CD31 immunohistochemical staining were performed on the wound surface.RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the acellular dermal matrix hydrogel had a porous structure,and the Fourier transform infrared spectrum showed that it had the same main components as the acellular dermal matrix.(2)Both acellular dermal matrix hydrogel and chitosan hydrogel had obvious hemostatic ability in vivo.In the in vitro coagulation experiments,the coagulation index of acellular dermal matrix hydrogel was significantly higher than that of chitosan hydrogel.(3)In the rat skin full-thickness defect model,both acellular dermal matrix hydrogel and chitosan hydrogel could improve the wound healing rate.Hematoxylin-eosin and Masson staining results showed that acellular dermal matrix hydrogel could reduce the infiltration of inflammatory cells in the center of the wound.Both acellular dermal matrix hydrogel and chitosan hydrogel could decrease scar width and increase collagen deposition rate.CD31 immunohistochemical staining results showed that both hydrogels could promote angiogenesis in the wound site.Immunofluorescence staining results showed that both hydrogels could reduce the proportion of M1 macrophages and increase the proportion of M2 macrophages,and the effect of acellular dermal matrix hydrogel was stronger than that of chitosan hydrogel.(4)The results show that the acellular dermal matrix hydrogel has good hemostatic properties and the ability to promote wound healing.

In recent years, the incidence of multiple primary lung cancer (MPLC) has been increasing, and it cannot be ignored in clinical practice. The treatment of MPLC is still controversial, but surgical treatment is recognized as the most important treatment. However, current studies have shown that the treatment of MPLC needs to develop multimodal treatment according to different patients. This review summarizes multiple treatment method for MPLC, including surgery, ablation, chemotherapy, radiotherapy, targeted therapy, and immunotherapy in order to enhance understanding of MPLC treatment.
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Humans ; Lung Neoplasms/surgery* ; Immunotherapy ; Combined Modality Therapy

Objective To investigate the levels of serum adrenomedullin precursor(pro-ADM),soluble leukocyte differentiation antigen 14 subtype(presepsin),and eosinophil chemotactic factor-1(Eotaxin-1)in patients with acute stroke(AS)complicated with pulmonary infection and their relationship with prognosis.Methods A total of 146 patients with AS admitted to the hospital from January 2022 to January 2024 were selected as the research subjects.According to whether the research subjects were complicated with pulmonary infection,they were divided into the infection group with 54 cases and the non-infection group with 92 cases.In addition,100 healthy individuals who underwent physical examinations in the hospital during the same period were selected as the control group.The prognosis of patients was evaluated using the modified Rankin scale score,which was divided into good prognosis and poor prognosis.The levels of serum pro-ADM,presepsin,Eotaxin-1 and C-reactive protein(CRP)were detected by enzyme-linked immunosorbent assay.Multivariate Logistic regression was used to analyze the influencing factors of AS complicated with pulmonary infection,and the receiver operating characteristic(ROC)curve was plotted to analyze the diagnostic value of serum CRP,pro-ADM,presepsin,and Eotaxin-1 levels for patients with AS complicated with pulmonary infection.Compare the levels of serum pro-ADM,presepsin and Eotaxin-1 in patients with different prognoses.The rela-tionship between the levels of serum pro-ADM,presepsin and Eotaxin-1 and the prognosis of patients was ana-lyzed by the Kaplan-Meier method.Results The levels of smoking history and serum CRP,pro-ADM,presep-sin,and Eotaxin-1 in the infection group were higher than those in the non-infection group and the control group,and the difference was statistically significant(P<0.05).The results of multivariate Logistic regres-sion analysis showed that the levels of serum CRP,pro-ADM,presepsin and Eotaxin-1 were the influencing factors of AS complicated with pulmonary infection(P<0.05).The results of the ROC curve analysis show that the area under the curve(AUC)of the combined diagnosis of AS complicated with pulmonary infection by serum pro-ADM,presepsin and Eotaxin-1 levels was higher than AUC of the individual diagnosis of CRP,pro-ADM,presepsin and Eotaxin-1(Z=3.921,2.445,2.825,3.076,P<0.05).The levels of serum pro-ADM,presepsin and Eotaxin-1 in patients with poor prognosis were higher than those in patients with good progno-sis,and the difference was statistically significant(P<0.05).The results of survival analysis by the Kaplan-Meier method showed that the survival rate of patients with high expression of serum pro-ADM,presepsin,and Eotaxin-1 was lower than that of patients with low expression(P<0.05).Conclusion The levels of ser-um pro-ADM,presepsin and Eotaxin-1 in patients with AS complicated with pulmonary infection are related to their prognosis.

AIM:To investigate the effects of the Qingfei-Jiedu-Huatan formula(QJHF)on damage to the lung vascular endothelial barrier induced by Klebsiella pneumoniae in mice with severe pneumonia,as well as to elucidate its underlying mechanisms.METHODS:Fifty-one C57BL/6J mice were randomly divided into control group(n=6),model group(n=15),QJHF group(n=15),and ceftriaxone sodium(CRO)group(n=15).Severe pneumonia was in-duced in the mice by a single tracheal intubation with 50 μL of 1×1011 CFU/mL Klebsiella pneumoniae on day 0.Six hours after modeling,the mice in QJHF and CRO groups received their respective treatments,while those in control and model groups were administered an equal volume of saline.All mice were sacrificed on day 3 after the end of gavage.Lung histo-pathological changes were assessed using hematoxylin-eosin(HE)staining.Levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in lung tissues were measured by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect CD11b+Ly6g+cells in bronchoalveolar lavage fluid(BALF).Proteomics and network pharma-cology analyses were conducted to elucidate the mechanisms of drug action.Western blot was conducted to assess the ex-pression levels of vascular endothelial cadherin(VE-cadherin),zonula occludens-1(ZO-1),occludin,vascular endothe-lial growth factor(VEGF),P38 mitogen-activated protein kinase(P38),and phosphorylated P38(p-P38)in lung tis-sues.RESULTS:Treatment with QJHF significantly attenuated the symptoms such as mental status and respiratory dis-tress,reduced mortality,mitigated lung tissue lesions,and decreased levels of IL-6,TNF-α,IL-1β,as well as BALF to-tal protein concentration,total cell count and neutrophil content in a mouse model of severe pneumonia(P＜0.05 or P＜0.01).Additionally,QJHF increased the expression of VE-cadherin,ZO-1 and occludin proteins in lung tissues.Pro-teomic analysis demonstrated that QJHF modulated the expression of 129 proteins in the lung tissues of mice suffering from severe pneumonia.Network pharmacology identified 328 potential targets associated with 14 major bioactive components of QJHF and 1 665 genes related to severe pneumonia,with 125 overlapping genes between the two datasets.The construc-tion of a protein-protein interaction(PPI)network,along with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the regulated proteins and overlapping genes,indicated that QJHF primarily in-fluenced the PI3K-Akt,MAPK and Rap1 signaling pathways,as well as VEGFR.Western blot analysis showed that QJHF significantly inhibited the expression of VEGF and P38 in lung tissues(P＜0.05 or P＜0.01).CONCLUSION:Treatment with QJHF attenuates severe pneumonia in mice,potentially by inhibiting VEGF/P38 signaling to protect the vascular endothelial barrier.

AIM:A mouse model of acute exacerbation of idiopathic pulmonary fibrosis(AE-IPF)was estab-lished.METHODS:One hundred and twenty male C57BL/6 mice were randomly divided into a negative control group,an IPF group,and an acute exacerbation of interstitial fibrosis(AE-IPF)group.The IPF group received a low dose(3 mg/kg)of bleomycin(BLM)by endotracheal drip on days 0,14,and 28.The AE-IPF group received a high dose(5 mg/kg)of BLM by endotracheal drip on day 56.The control group received an equal volume of saline at different time points.The AE-IPF group was injected with a high dose(5 mg/kg)of BLM via tracheal drip on day 56 on top of the initial IPF induction,while the control group received equal amounts of saline at different time points.Experiments were con-ducted on the 57th,59th,63rd,and 70th days after the initial modeling.Mice were observed for general conditions,CT imaging changes,HE,and Masson staining to assess the degree of alveolitis and fibrosis in lung tissues.Lung function,hydroxyproline(HYP)content in lung tissues,and interleukin-6(IL-6)content in bronchoalveolar lavage fluid(BALF)were also measured.RESULTS:Mice in the AE-IPF group exhibited wheezing,shortness of breath,dyspnea,and weight loss.CT imaging revealed that IPF group mice showed patchy,subpleural reticular fuzzy shadows with irregular thickening of interlobular septa and intralobular linear shadows,along with tractional bronchiectasis.In the AE-IPF group,new ground-glass shadows and solid shadows appeared in addition to the IPF features.AE-IPF group mice demon-strated decreased lung function,elevated lung index,and acute pulmonary edema.HE and Masson staining of AE-IPF group mice showed consistent pathological manifestations of AE-IPF.HYP content in lung tissues,total cell count in BALF,and IL-6 concentration were significantly higher in the AE-IPF group compared to the control group(P<0.05).CONCLUSION:The use of multiple tracheal drip administrations of bleomycin successfully established an AE-IPF ani-mal model in mice.The 63rd day of the experiment was identified as the optimal observation point,as it exhibited the most significant pathological features and clinical symptoms.This model provides ideal conditions for studying AE-IPF patho-genesis and evaluating therapeutic efficacy.

Objective To investigate the therapeutic effects of the newly developed phosphodiesterase 5 inhibitor,CPD1,on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,and its impact on activation of the autophagy signaling pathway in myocardial tissue.Methods Male Sprague Dawley rats weighing 180～200 g were divided randomly into five groups:Control,Sham,model(AAC),CPD1 treatment(AAC-CPD1,5 mg/kg),and sildenafil treatment(AAC-Sif,20 mg/kg)groups.Rats in all groups except the Control group underwent blunt dissection of the abdominal aorta at the branch point of the left renal artery.Rats in the AAC and treatment groups also underwent constriction and ligation surgery,while rats in the Sham group underwent dissection without ligation.After 3 days of modeling,rats in the treatment groups received either CPD1 or sildenafil via gavage,while rats in the Control,Sham,and AAC groups received an equal volume of physiological saline by gavage,once daily for 8 weeks.Small-animal ultra-high-resolution echocardiography and left ventricular catheterization were employed to assess left heart function and the heart mass index,and expression levels of the hypertrophy indicator,atrial natriuretic peptide(ANP),the key autophagy pathway factor,p62,and LC3A/B in rat left heart tissue were evaluated by Western blot and reverse transcription-polymerase chain reaction.Results Abdominal aortic stenosis affected left heart function in rats,characterized by an increased cardiac mass index and significant enlargement of myocardial cell cross-sectional area.ANP expression levels in left heart tissue were significantly elevated(P＜0.05),while autophagy signaling activity was reduced,with notable accumulation of LC3Ⅰprotein and reduced conversion to LC3Ⅱ.Expression levels of p62 protein were significantly increased.CPD1 and sildenafil significantly improved left ventricular function in AAC rats,reduced cardiac hypertrophy,inhibited expression levels of ANP and p62 proteins(P＜0.05),activated autophagy signaling,and promoted the conversion of LC3Ⅰ to LC3Ⅱ.Notably,low-dose CPD1 treatment was equivalent to high-dose sildenafil.Conclusions CPD1 promotes the activation of the autophagy signaling pathway in left heart tissue,inhibits the expression of p62 and ANP,reduces the cross-sectional area of myocardial cells,and improves pathological myocardial hypertrophy and left heart function impairment caused by AAC.CPD1 also has the advantage of a lower effective dose compared with sildenafil,offering a new treatment option for pathological myocardial hypertrophy.

AIM:To investigate the effects of the Qingfei-Jiedu-Huatan formula(QJHF)on damage to the lung vascular endothelial barrier induced by Klebsiella pneumoniae in mice with severe pneumonia,as well as to elucidate its underlying mechanisms.METHODS:Fifty-one C57BL/6J mice were randomly divided into control group(n=6),model group(n=15),QJHF group(n=15),and ceftriaxone sodium(CRO)group(n=15).Severe pneumonia was in-duced in the mice by a single tracheal intubation with 50 μL of 1×1011 CFU/mL Klebsiella pneumoniae on day 0.Six hours after modeling,the mice in QJHF and CRO groups received their respective treatments,while those in control and model groups were administered an equal volume of saline.All mice were sacrificed on day 3 after the end of gavage.Lung histo-pathological changes were assessed using hematoxylin-eosin(HE)staining.Levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in lung tissues were measured by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect CD11b+Ly6g+cells in bronchoalveolar lavage fluid(BALF).Proteomics and network pharma-cology analyses were conducted to elucidate the mechanisms of drug action.Western blot was conducted to assess the ex-pression levels of vascular endothelial cadherin(VE-cadherin),zonula occludens-1(ZO-1),occludin,vascular endothe-lial growth factor(VEGF),P38 mitogen-activated protein kinase(P38),and phosphorylated P38(p-P38)in lung tis-sues.RESULTS:Treatment with QJHF significantly attenuated the symptoms such as mental status and respiratory dis-tress,reduced mortality,mitigated lung tissue lesions,and decreased levels of IL-6,TNF-α,IL-1β,as well as BALF to-tal protein concentration,total cell count and neutrophil content in a mouse model of severe pneumonia(P＜0.05 or P＜0.01).Additionally,QJHF increased the expression of VE-cadherin,ZO-1 and occludin proteins in lung tissues.Pro-teomic analysis demonstrated that QJHF modulated the expression of 129 proteins in the lung tissues of mice suffering from severe pneumonia.Network pharmacology identified 328 potential targets associated with 14 major bioactive components of QJHF and 1 665 genes related to severe pneumonia,with 125 overlapping genes between the two datasets.The construc-tion of a protein-protein interaction(PPI)network,along with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the regulated proteins and overlapping genes,indicated that QJHF primarily in-fluenced the PI3K-Akt,MAPK and Rap1 signaling pathways,as well as VEGFR.Western blot analysis showed that QJHF significantly inhibited the expression of VEGF and P38 in lung tissues(P＜0.05 or P＜0.01).CONCLUSION:Treatment with QJHF attenuates severe pneumonia in mice,potentially by inhibiting VEGF/P38 signaling to protect the vascular endothelial barrier.

Objective To investigate the therapeutic effects of the newly developed phosphodiesterase 5 inhibitor,CPD1,on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,and its impact on activation of the autophagy signaling pathway in myocardial tissue.Methods Male Sprague Dawley rats weighing 180～200 g were divided randomly into five groups:Control,Sham,model(AAC),CPD1 treatment(AAC-CPD1,5 mg/kg),and sildenafil treatment(AAC-Sif,20 mg/kg)groups.Rats in all groups except the Control group underwent blunt dissection of the abdominal aorta at the branch point of the left renal artery.Rats in the AAC and treatment groups also underwent constriction and ligation surgery,while rats in the Sham group underwent dissection without ligation.After 3 days of modeling,rats in the treatment groups received either CPD1 or sildenafil via gavage,while rats in the Control,Sham,and AAC groups received an equal volume of physiological saline by gavage,once daily for 8 weeks.Small-animal ultra-high-resolution echocardiography and left ventricular catheterization were employed to assess left heart function and the heart mass index,and expression levels of the hypertrophy indicator,atrial natriuretic peptide(ANP),the key autophagy pathway factor,p62,and LC3A/B in rat left heart tissue were evaluated by Western blot and reverse transcription-polymerase chain reaction.Results Abdominal aortic stenosis affected left heart function in rats,characterized by an increased cardiac mass index and significant enlargement of myocardial cell cross-sectional area.ANP expression levels in left heart tissue were significantly elevated(P＜0.05),while autophagy signaling activity was reduced,with notable accumulation of LC3Ⅰprotein and reduced conversion to LC3Ⅱ.Expression levels of p62 protein were significantly increased.CPD1 and sildenafil significantly improved left ventricular function in AAC rats,reduced cardiac hypertrophy,inhibited expression levels of ANP and p62 proteins(P＜0.05),activated autophagy signaling,and promoted the conversion of LC3Ⅰ to LC3Ⅱ.Notably,low-dose CPD1 treatment was equivalent to high-dose sildenafil.Conclusions CPD1 promotes the activation of the autophagy signaling pathway in left heart tissue,inhibits the expression of p62 and ANP,reduces the cross-sectional area of myocardial cells,and improves pathological myocardial hypertrophy and left heart function impairment caused by AAC.CPD1 also has the advantage of a lower effective dose compared with sildenafil,offering a new treatment option for pathological myocardial hypertrophy.

AIM:A mouse model of acute exacerbation of idiopathic pulmonary fibrosis(AE-IPF)was estab-lished.METHODS:One hundred and twenty male C57BL/6 mice were randomly divided into a negative control group,an IPF group,and an acute exacerbation of interstitial fibrosis(AE-IPF)group.The IPF group received a low dose(3 mg/kg)of bleomycin(BLM)by endotracheal drip on days 0,14,and 28.The AE-IPF group received a high dose(5 mg/kg)of BLM by endotracheal drip on day 56.The control group received an equal volume of saline at different time points.The AE-IPF group was injected with a high dose(5 mg/kg)of BLM via tracheal drip on day 56 on top of the initial IPF induction,while the control group received equal amounts of saline at different time points.Experiments were con-ducted on the 57th,59th,63rd,and 70th days after the initial modeling.Mice were observed for general conditions,CT imaging changes,HE,and Masson staining to assess the degree of alveolitis and fibrosis in lung tissues.Lung function,hydroxyproline(HYP)content in lung tissues,and interleukin-6(IL-6)content in bronchoalveolar lavage fluid(BALF)were also measured.RESULTS:Mice in the AE-IPF group exhibited wheezing,shortness of breath,dyspnea,and weight loss.CT imaging revealed that IPF group mice showed patchy,subpleural reticular fuzzy shadows with irregular thickening of interlobular septa and intralobular linear shadows,along with tractional bronchiectasis.In the AE-IPF group,new ground-glass shadows and solid shadows appeared in addition to the IPF features.AE-IPF group mice demon-strated decreased lung function,elevated lung index,and acute pulmonary edema.HE and Masson staining of AE-IPF group mice showed consistent pathological manifestations of AE-IPF.HYP content in lung tissues,total cell count in BALF,and IL-6 concentration were significantly higher in the AE-IPF group compared to the control group(P<0.05).CONCLUSION:The use of multiple tracheal drip administrations of bleomycin successfully established an AE-IPF ani-mal model in mice.The 63rd day of the experiment was identified as the optimal observation point,as it exhibited the most significant pathological features and clinical symptoms.This model provides ideal conditions for studying AE-IPF patho-genesis and evaluating therapeutic efficacy.